Defibrillation testing is often performed during insertion of implantable cardioverter-defibrillators (ICDs) to confirm shock efficacy without good prospective data to suggest that this procedure improves outcomes. Our analysis included patients in the ICD arm of the SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial). We concluded that: 1) low baseline defibrillation thresholds (DFTs) were obtained in patients with optimally treated heart failure during ICD implantation for primary prevention of sudden death; 2) first shock efficacy for clinical ventricular tachyarrhythmias was high regardless of baseline DFT; and 3) baseline DFT did not predict long-term mortality or shock efficacy.

Abstract

Background Defibrillation testing is often performed during insertion of ICDs to confirm shock efficacy. There are no prospective data to suggest that this procedure improves outcomes when modern ICDs are implanted for primary prevention of sudden death.

Methods The analysis included the 811 patients who were randomized to the ICD arm of the SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial) and had the device implanted. The DFT testing protocol in SCD-HeFT was designed to limit shock testing in a primary prevention heart failure population.

Results Baseline DFT data were available for 717 patients (88.4%). All 717 patients had a DFT of ≤30 J, the maximum output of the device in this study. The DFT was ≤20 J in 97.8% of patients. There was no survival difference between patients with a lower DFT (≤10 J, n = 547) and a higher DFT (>10 J, n = 170) (p = 0.41). First shock efficacy was 83.0% for the first clinical ventricular tachyarrhythmia event; there were no differences in shock efficacies when the cohort was subdivided by baseline DFT.

Conclusions Low baseline DFTs were obtained in patients with stable, optimally treated heart failure during ICD implantation for primary prevention of sudden death. First shock efficacy for ventricular tachyarrhythmias was high regardless of baseline DFT testing results. Baseline DFT testing did not predict long-term mortality or shock efficacy in this study.

Implantable cardioverter-defibrillators (ICDs) have been shown to reduce mortality when used for primary prevention of sudden cardiac death (SCD). This benefit has been shown in patients with reduced systolic function caused by both ischemic (1,2) and nonischemic cardiomyopathies (2).

Electrical defibrillation of ventricular tachyarrhythmias is a probabilistic event in both animal and human studies, especially at the margin of efficacy (3,4). Increased defibrillation energy generally results in a greater chance of success, a relationship expressed with a sinusoidal curve. The defibrillation threshold (DFT) has been defined variously, either as the amount of energy required to defibrillate 50% of induced ventricular fibrillation (VF) episodes (5) or as the lowest amount of energy required to defibrillate (6). Because of the potentially catastrophic nature of defibrillation failure, physicians implanting ICDs often attempt to demonstrate the efficacy of the device by inducing VF and determining the DFT or by performing limited shock testing to determine a sufficient safety margin. Some investigators have advocated for “shock-free” DFT testing to determine the upper limit of vulnerability as an alternative to inducing VF (7). These practices originate from an earlier era in ICD technology when defibrillation with monophasic waveforms and less effective electrode systems were more of a challenge. Modern ICDs defibrillate effectively as a result of optimally structured biphasic shock waveforms that use an active can electrode system (8–11). Neither DFT testing nor upper limit of vulnerability testing has been definitively linked to improved outcomes in a prospective trial using current technology.

Most primary prevention ICD trials (1,2) included some type of DFT testing as part of the ICD procedural protocol, although specific DFT testing protocols have not been well described. Although current literature generally recommends DFT testing, evidence for this practice is minimal (6,12). Limited prospective data are available from a single center using monophasic waveform technology in a small cohort, and thus it is unclear whether these data can be used to justify the practice of DFT testing with modern devices (13). More recent publications continue to advocate DFT testing, but these studies failed to show increased mortality in those with an inadequate DFT safety margin (14–16). Moreover, additional surgical procedures required to improve DFTs, such as ICD generator repositioning, lead repositioning, or subcutaneous array placement in addition to extensive shock testing, may carry more risk to the patient than the laboratory finding of an increased DFT. In a recent review (17), DFT testing was noted as the “legal standard of care,” but the investigators suggest that testing is clearly indicated and safe in 45% of ICD recipients, is contraindicated in 5%, and neither its safety nor indication is clear in the remaining 50%. Published guidelines do not officially recommend DFT testing (18), and the Centers for Medicare and Medicaid Services make no specific recommendations for or against testing (19).

The SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial) is the largest and longest-duration randomized, prospective, primary prevention trial in both ischemic and nonischemic heart failure patients to date. The DFT testing protocol in this trial called for only minimal shock testing; ICD implantation was recommended regardless of the outcome. The purpose of the present study is to examine the relationship between DFT testing results and clinical outcomes.

Methods

The SCD-HeFT methods and results have been described in detail elsewhere (2,20). The SCD-HeFT study was a National Institutes of Health-sponsored multicenter clinical trial in which 2,521 patients without a history of sustained ventricular tachycardia (VT) or cardiac arrest were randomly assigned in equal proportions to receive an ICD, amiodarone, or placebo. The enrolled patients had chronic moderate heart failure (New York Heart Association functional class II or III) and a left ventricular ejection fraction ≤35%. The study protocol required optimal medical therapy with angiotensin-converting enzyme inhibitor or angiotensin-receptor antagonist, beta-receptor antagonist, and aldosterone-antagonist drugs as prescribed by current heart failure guidelines before randomization. Outpatient ICD implantation was recommended.

The ICDs implanted in SCD-HeFT were intentionally limited to single-lead devices because patients with indications for dual-chamber pacing were excluded by protocol. Most patients (94%) received a Medtronic Micro Jewel II Model 7223 device (Minneapolis, Minnesota), whereas the remaining 6% received another Medtronic single-lead device. Maximum device output was 30 J. No biventricular devices were permitted at implantation. The ICD was uniformly programmed with a detection rate of ≥188 beats/min. Therapy was programmed to a single tachyarrhythmia zone, shock-only mode. No antitachycardia pacing was permitted to minimize the potential for accelerating tachyarrhythmias or for treating nonsustained ventricular tachycardia in patients who were not known to have VT. Bradycardia pacing was set to 50 beats/min with a hysteresis of 34 beats/min.

The SCD-HeFT DFT testing protocol sought to minimize the number of VF inductions to balance the risk of testing against perceived benefit in a population that had, at the time of trial enrollment, no known indication for ICD therapy. The VF was induced with a T-wave shock (21). After detection of VF, the first defibrillation shock of 20 J was delivered. If unsuccessful, a transthoracic rescue shock was applied. A 5-min rest period was recommended between VF inductions. If the first defibrillation attempt at 20 J was successful, the second defibrillation attempt was to be performed with a 10-J shock. If the first attempt of 20 J was unsuccessful, the second attempt was to be performed with a 30-J shock. No further VF inductions were recommended regardless of defibrillation success after the second induction. In this trial, the DFT was defined as the lowest successful shock output. The ICD therapy was programmed with the first shock set 10 J over the DFT (if ≤20 J) followed by maximum output shocks for all remaining therapies. The shock waveform was programmed bipolar with the right ventricular coil anodal (B>AX) for therapies 1 through 4 with reversed polarity for therapies 5 and 6. The ICD was implanted regardless of DFT testing results, and the use of alternative lead systems or devices was strongly discouraged to minimize risk and to preserve the uniformity of the study protocol.

The ICD data were routinely downloaded at 3-month follow-up visits and after known ICD therapy. Post-mortem ICD interrogation was recommended after all patient deaths. The ICD electrogram (EGM) data were sent electronically to the ICD EGM core laboratory. Two members of the ICD EGM Committee independently reviewed each shock episode and categorized each rhythm before and after each shock according to pre-specified criteria (22). Rhythms were categorized based on data from both R-R interval plots and EGM recordings, when available. The EGM Committee was blinded to patient outcome and all clinical data. Disagreements were adjudicated by the full EGM Committee.

Only the first appropriate shock experienced by a patient for VF or VT was considered in this analysis. This was chosen by study design, because baseline DFT testing was considered to most likely relate to a first arrhythmic event rather than subsequent events, in which events such as progressive heart failure, ischemia, the potential adverse effect of recurrent shocks, or new antiarrhythmic therapy could be confounding factors. Shock success was defined as termination of the detected VF or VT, as determined by intracardiac post-shock EGM recording, and not by clinical outcome. This analysis includes only those patients who had VT or VF events detected with the SCD-HeFT–specified programming protocol. Arrhythmia events detected only because of protocol deviation with a second zone of therapy programmed with antitachycardia pacing are not included because of the unknown effects of delaying shock therapy due to pacing interventions.

Statistical analysis

Overall cumulative survival was analyzed with the Kaplan-Meier method after arbitrarily dividing the ICD cohort into low and high DFT groups (23). Survival between the 2 groups was compared using a Cox regression model (24). Covariates included in this model were age, gender, heart failure etiology, New York Heart Association functional class, time since heart failure diagnosis, ejection fraction, 6-min walk distance, systolic blood pressure, diabetes, angiotensin-converting enzyme inhibitor use, digoxin use, mitral valve regurgitation, renal insufficiency, substance abuse, baseline electrocardiographic intervals, and the Duke Activity Status Index (25). There are no published data available to estimate the mortality benefit, if any, that DFT testing provides. However, assuming an alpha of 0.05 (2-sided), we would have 80% power for detecting a 38% difference in mortality between groups with the 146 deaths in our cohort.

A sensitivity analysis was performed to account for patients without baseline DFT testing data available by including this group first in the high-DFT group, followed by including them in the low-DFT group and repeating the analyses.

We tested for association between baseline DFT testing results and defibrillation success for spontaneous VF or VT episodes, using the Fisher exact test (26). A p value of <0.05 was considered significant. For all analyses, commercially available statistical package software was used (SAS version 8.2, SAS Institute Inc., Cary, North Carolina, and SPSS version 11.5, SPSS, Inc., Chicago, Illinois). Patients who had their ICD explanted were included in the ICD group for analysis in an intention-to-treat manner.

The investigators had full access to the data and take responsibility for its integrity. All investigators have read and agree to the article as written.

Results

Baseline ICD implantation and DFT data

Of the 2,521 patients enrolled in the SCD-HeFT, 829 were randomized to the ICD arm. Of those, 17 patients refused ICD implantation and 1 patient died before implantation. Therefore, 811 patients were included in this study. The median follow-up for all surviving patients was 45.5 months. All surviving patients were followed up for at least 2 years, and vital status was known for all patients at the time of last follow-up. Of those with an ICD implanted, 31 (3.8%) had their ICD removed and not replaced during follow-up because of device complications (n = 8), other medical problems (n = 3), or heart transplantation (n = 20).

Baseline DFT testing data were available from 717 patients (88.4% of those with an ICD). Of the remaining 94 patients, no data were received by the ICD event core laboratory for 88 patients and ICD testing was intentionally not performed in 6 cases. Of the 717 patients, most had DFT testing performed according to protocol, although 26 (3.6%) had testing performed at additional energy levels. All of the 717 patients were defibrillated at ≤30 J and 97.8% had successful defibrillation at ≤20 J (Fig. 1).

Patients with a DFT of >10 J all had their first shock energy programmed to 30 J. Patients with a DFT of ≤10 J had the first shock programmed to 20 J (86.8%) or 30 J (13.2%), the latter because of investigator-elected protocol deviation.

Survival associated with baseline DFT results

The patients were divided into a low-DFT group (≤10 J) and a high-DFT group (>10 J). There were 113 deaths in the low-DFT group (overall mortality 20.7%) and 33 deaths in the high-DFT group (overall mortality 19.4%.) After adjusting for baseline prognostic variables, there was no difference in overall survival between the 2 groups (hazard ratio [HR] for DFT >10: 1.19; 95% confidence interval [CI]: 0.72 to 1.58, p = 0.41) (Fig. 2). The results were not altered, regardless of whether the 94 patients with missing data were considered in the high-DFT or low-DFT group, (p = 0.75 and p = 0.13, respectively).

Curves show no difference in all-cause mortality when patients with an ICD were divided by high-DFT and low-DFT groups (hazard ratio for DFT >10: 1.19; 95% confidence interval: 0.72 to 1.58; p = 0.41). Abbreviations as in Figure 1.

Shock efficacy and baseline DFT result

Of the 811 ICD patients, 182 (22.4%) experienced at least 1 ICD-detected episode of VT or VF during follow-up. The first shock delivered during the first occurrence of either VF or VT (whichever came first in patients with recurrent events) was successful in 151 of these patients (83.0%). The relationship between first shock efficacy was similarly high regardless of whether patients had a baseline DFT of ≤10 J, ≥11 to ≤20 J, or >20 J. There was no significant difference between first shock efficacy rates in these groups (82.6%, 81.0%, and 100% respectively, p = 0.88) (Table 1). Patients without baseline DFT testing data had a first shock efficacy of 90.4%, which was not significantly different from those with DFT data available (p = 0.13).

Implant DFTs, Appropriate Shocks, and Efficacy: First Shock Efficacy for the First VT or VF Event According to Baseline DFT

Rhythm outcome in first shock failures

Unsuccessful shocks were analyzed to determine the eventual rhythm outcome. Of 31 patients with an unsuccessful first shock, in only 3 patients did all subsequent shocks fail; these 3 patients are known to have died on the day of the ICD-detected rhythm. The remaining 28 patients are known to have survived this event. In 6 of these 28 cases, the rhythm self-terminated after the first failed shock. In 8 more cases, a second or third shock was successful. In the remaining 14 cases, the arrhythmia fell below the detection rate and no further EGM data were recorded; presumably, these arrhythmias self-terminated given that clinical outcome follow-up showed that these patients were alive after the event.

Discussion

The present study represents the only prospective analysis of the relationship between DFT testing and outcomes in patients treated with modern ICDs. There are several significant findings. First, in a primary prevention ICD patient population treated with good heart failure medical therapy, implant defibrillation efficacy for induced VF was well within the accepted safety margin for the vast majority of patients. Second, the first shock success for spontaneous VT or VF events was good (>80%) regardless of implant DFT. Finally, survival after a first appropriate VT or VF event was similarly high for patients with high or low baseline DFT testing.

Of the failed shocks analyzed here, 9.7% were followed immediately by death. These occurred in hospitalized patients who had significant clinical deterioration in their cardiac status. The ICDs do not completely eliminate the risk of sudden death, particularly in those with progressive heart failure, but most failed shocks did not result in death. There are data to suggest that many shock failures occur in the setting of electrical–mechanical dissociation (27), a phenomenon not likely to be related to baseline DFT testing.

It is remarkable that all patients for whom data were available had successful implant defibrillation for induced VF of ≤30 J. This may reflect a stable outpatient cohort of patients appropriately treated with good heart failure medications. Therefore, our results may not be applicable to a more ill patient population. It is often in the more ill patient that the adverse effects of VF induction are considered a reason not to perform testing. That DFT testing may be irrelevant to successful ICD treatment of spontaneous VT or VF may justify a paradigm shift in the traditional approach to these patients. Although we observed first shock failure in approximately 20% of patients, this was only fatal in 3 patients, all of whom were hospitalized at the time for progressive heart failure. Our study cannot make specific recommendations for patients who are found to have an implant DFT of greater than the output of the device, although our data suggest that there will be a very small number of such patients in this study population. It is interesting to note that the 3 patients who had an appropriate shock for VT or VF and had no DFT safety margin (i.e., a DFT of 30 J) during ICD implantation, had 100% effective shocks, again questioning the utility of DFT testing in this population.

Shock efficacy must also take into consideration the critical components of ICD technology and shock delivery. Shock energy alone is known to be a very poor surrogate for defibrillation efficacy, and many features of waveform design (i.e., capacitance, phase duration, waveform tilt, peak voltage, and peak current levels) as well as electrode design and location (e.g., material, French size, location, and ICD surface area) can influence defibrillation (6). Early studies of defibrillation evaluating these components have resulted in modern-day devices that are highly efficient at delivering shock energy. As a consequence, the findings of this study may not necessarily extend to other ICDs with significantly different energy delivery systems.

Study limitations

This study has several limitations. First, not all data on implant testing were available to the ICD event core laboratory. Whether the data were not immediately sent and therefore were overwritten or were never saved at all is not known. Second, because few patients had a high DFT, conclusions regarding the outcomes of patients without the usual DFT safety margin cannot be made. Third, defibrillation testing for induced VF may not predict cardioversion efficacy for ventricular tachycardia. In this study, only 71 of the 182 patients (39.0%) with an appropriate shock had VF. Differences may exist between VF and VT; however, because of small numbers, statistical analysis of these subgroups was not performed. Comparing outcomes at implant testing for induced VF with that of spontaneous VT may be fundamentally limiting. Finally, the relatively small number of deaths in our cohort reduces our ability to detect small changes in survival related to DFT testing.

Conclusions

This study presents unique data supporting a limited approach to DFT testing in stable outpatients with New York Heart Association functional class II or III heart failure. Our results challenge the commonly accepted requirement to perform routine DFT testing during ICD implantation for primary prevention of sudden cardiac death. Given the lack of correlation between baseline DFT testing and either shock efficacy or survival, future studies should determine whether DFT testing in this population should be abandoned altogether.

Acknowledgment

The authors gratefully acknowledge Rebecca Conklin for her assistance in editing this manuscript.

Footnotes

The SCD-HeFT study was supported by National Heart, Lung, and Blood Institute (NHLBI) grants UO1 HL55766, UO1 HL55297, and UO1 HL55496, the National Institutes of Health (NIH), Medtronic, and Wyeth-Ayerst Laboratories. Dr. Poole has received lecture fees from Medtronic and Boston Scientific/Guidant; consulting fees from Phillips; and grants from Biotronik and the National Institutes of Health/National Heart, Lung, and Blood Institute. Dr. Callans has received research grants from Biosense Webster, St. Jude Medical, and Siemens Acuson, and speaking fees from Biosense Webster, St. Jude Medical., and Boston Scientific, and has served as a consultant for St. Jude Medical. Dr. Reddy has received consulting fees and lecture fees from Boston Scientific/Guidant, Medtronic, and St. Jude Medical, and has stock options in Cambridge Heart. Dr. Marchlinski has received consulting fees, lecture fees, and grant support from Medtronic, Boston Scientific/Guidant, and St. Jude Medical. Dr Raitt has received research funding from the Veterans Affairs Administration. Dr. Talajic has received consulting fees and lecture fees from Medtronic and lecture fees from St. Jude Medical. Dr. Wilber has received research support and consulting fees from Medtronic, Boston Scientific/Guidant, Inc., and St. Jude Medical. Jill Anderson has received lecture fees from Boston Scientific/Guidant, Inc. Dr. Mark has received consulting fees from Aventis, AstraZeneca, Medtronic, and Novartis, and research grants from the NIH/NHLBI, NIH/Agency for Healthcare Research and Quality, Proctor and Gamble, Pfizer, Medtronic, Alexion Pharmaceuticals, and Medicure; he has also received fees as editor for the American Heart Journal from Mosby, Inc. Dr. Lee has received research funding from NIH/NHLBI, research funding from Medtronic, and consulting fees from Medtronic. Dr. Bardy has received research funding from the NIH, research funding from Medtronic, consultant fees and research funding from Phillips Medical Systems, and board position, equity, and intellectual property with Cameron Health.

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